DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1320 that H. pylori plays a major etiopathogenic role in the majority
of peptic ulcers, prevention of relapse is focused on eliminating
this organism from the stomach. Chronic acid suppression, once
the mainstay of ulcer prevention, now is used mainly in patients
who are H. pylori–negative or, in some cases, for maximum prevention
of recurrence in patients who have had life-threatening
complications.
Intravenous pantoprazole or lansoprazole clearly is the preferred
therapy in patients with acute bleeding ulcers. The theoretical
benefit of maximal acid suppression in this setting is to accelerate
healing of the underlying ulcer. In addition, a higher gastric pH
enhances clot formation and retards clot dissolution.
SECTION VI
DRUGS AFFECTING GASTROINTESTINAL FUNCTION
Treatment of Helicobacter pylori Infection. H. pylori,
a gram-negative rod, has been associated with gastritis
and the subsequent development of gastric and duodenal
ulcers, gastric adenocarcinoma, and gastric B-cell
lymphoma (Suerbaum and Michetti, 2002). Because of
the critical role of H. pylori in the pathogenesis of peptic
ulcers, to eradicate this infection is standard care in
patients with gastric or duodenal ulcers. Provided that
patients are not taking NSAIDs, this strategy almost
completely eliminates the risk of ulcer recurrence.
Eradication of H. pylori also is indicated in the treatment
of mucosa-associated lymphoid tissue lymphomas
of the stomach, which can regress significantly
after such treatment.
Many regimens for H. pylori eradication have
been proposed. Evidence-based literature review suggests
that the ideal regimen in this setting should achieve a
cure rate of at least 80%. Five important considerations
influence the selection of an eradication regimen (Chey
and Wong, 2007; Graham, 2000) (Table 45–5). First,
single-antibiotic regimens are ineffective in eradicating
H. pylori infection and lead to microbial resistance.
Combination therapy with two or three antibiotics (plus
acid-suppressive therapy) is associated with the highest
rate of H. pylori eradication. Second, a proton pump
inhibitor or H 2
receptor antagonist significantly
enhances the effectiveness of H. pylori antibiotic regimens
containing amoxicillin or clarithromycin. Third,
a regimen of 10-14 days of treatment appears to be better
than shorter treatment regimens; in the U.S., a
14-day course of therapy generally is preferred. Fourth,
poor patient compliance is linked to the medicationrelated
side effects experienced by as many as half of
patients taking triple-agent regimens, and to the inconvenience
of three- or four-drug regimens administered
several times per day. Packaging that combines the
daily doses into one convenient unit is available and
may improve patient compliance (Table 45–5). Finally,
the emergence of resistance to clarithromycin and
Table 45–5
Therapy of Helicobacter pylori Infection
Triple therapy × 14 days: Proton pump inhibitor +
clarithromycin 500 mg plus metronidazole 500 mg or
amoxicillin 1 g twice a day (tetracycline 500 mg
can be substituted for amoxicillin or metronidazole)
Quadruple therapy × 14 days: Proton pump inhibitor
twice a day + metronidazole 500 mg three times
daily plus bismuth subsalicylate 525 mg + tetracycline
500 mg four times daily
or
H 2
receptor antagonist twice a day plus bismuth
subsalicylate 525 mg + metronidazole 250 mg +
tetracycline 500 mg four times daily
Dosages:
Proton pump inhibitors: H 2
receptor antagonists:
Omeprazole: 20 mg Cimetidine: 400 mg
Lansoprazole: 30 mg Famotidine: 20 mg
Rabeprazole: 20 mg Nizatidine: 150 mg
Pantoprazole: 40 mg Ranitidine: 150 mg
Esomeprazole: 40 mg
See Chey and Wong, 2007.
metronidazole increasingly is recognized as an important
factor in the failure to eradicate H. pylori.
Clarithromycin resistance is related to mutations that
prevent binding of the antibiotic to the ribosomes of the
pathogen and is an all-or-none phenomenon. In contrast,
metronidazole resistance is relative rather than
absolute and may involve several adaptations by the
bacteria. In the presence of in vitro evidence of resistance
to metronidazole, amoxicillin should be used
instead. In areas with a high frequency of resistance to
clarithromycin and metronidazole, a 14-day quadrupledrug
regimen (three antibiotics combined with a proton
pump inhibitor) generally is effective therapy.
NSAID-Related Ulcers. Chronic NSAID users have a
2-4% risk of developing a symptomatic ulcer, GI bleeding,
or perforation. Ideally, NSAIDs should be discontinued
in patients with an ulcer if at all possible. If
continued therapy is needed, selective COX-2 inhibitors
may be considered, although this does not eliminate the
risk of subsequent ulcer formation and the possible
association of these drugs with adverse cardiovascular
events mandates caution (Chapter 34). Moreover, any
GI benefit of selective COX-2 inhibitors is lost if the
patient is also taking low-dose aspirin. Healing of ulcers
despite continued NSAID use is possible with the use